Discovery of C-Linked Nucleoside Analogues with Antiviral Activity against SARS-CoV-2.

The recent COVID-19 pandemic underscored the limitations of currently available direct-acting antiviral treatments against acute respiratory RNA-viral infections and stimulated major research initiatives targeting anticoronavirus agents. Two novel nsp5 protease (MPro) inhibitors have been approved, nirmatrelvir and ensitrelvir, along with two existing nucleos(t)ide analogues repurposed as nsp12 polymerase inhibitors, remdesivir and molnupiravir, but a need still exists for therapies with improved potency and systemic exposure with oral dosing, better metabolic stability, and reduced resistance and toxicity risks. Herein, we summarize our research toward identifying nsp12 inhibitors that led to nucleoside analogues 10e and 10n, which showed favorable pan-coronavirus activity in cell-infection screens, were metabolized to active triphosphate nucleotides in cell-incubation studies, and demonstrated target (nsp12) engagement in biochemical assays.

Riboflavin (vitamin B2) sensitized photooxidation of ascorbic acid (vitamin C): A kinetic study.

Ascorbic acid (AH2) photoxidation sensitized by riboflavin (RF) has been studied between pH 2.0 and 12.0 in ambient air and anaerobic environment using UV and visible irradiation sources. The kinetics of AH2 degradation in aqueous medium along with RF is found to be first-order for its photodegradation. AH2 photolysis rate constants in aerobic and anaerobic conditions with RF (1.0-5.0 × 10-5 M) are 0.14-3.89 × 10-2 and 0.026-0.740 × 10-2 min-1, respectively. The rate constants (k2) of second-order kinetics for AH2 and RF photochemical interaction in aerobic and anaerobic conditions are in the range of 0.24-3.70 to 0.05-0.70 × 10-3 M-1 min-1, respectively, which manifests that increasing the RF concentration also increases the rate of photodegradation (photooxidation) of AH2. The k2 versus pH graph is bell-shaped which indicates that increasing the pH increases photolytic degradation rate of AH2 with RF. Increasing the pH results in the increased ionization of AH2 (ascorbyl anion, AH-) and redox potential which leads to the higher rates of photodegradation of AH2. Two-component spectrophotometric (243 and 266 nm, AH2 and RF, respectively) and high-performance liquid chromatography (HPLC) methods have been used to determine the concentration of AH2 and RF in pure and degraded solutions. The results obtained from these two methods are compared using a student t-test which showed no noteworthy difference between them.

The role of thermal tolerance in determining elevational distributions of four arthropod taxa in mountain ranges of southern Asia.

Understanding the role of thermal tolerances in determining species distributions is important for assessing species responses to climate change. Two hypotheses linking physiology with species distributions have been put forward-the climatic variability hypothesis and the climatic extreme hypothesis. The climatic variability hypothesis predicts the selection of individuals with broad thermal tolerance in more variable climatic conditions and the climatic extreme hypothesis predicts the selection of individuals with extreme thermal tolerance values under extreme climatic conditions. However, no study has tested the predictions of these hypotheses simultaneously for several taxonomic groups along elevational gradients. Here, we related experimentally measured critical thermal maxima, critical thermal minima and thermal tolerance breadths for 15,187 individuals belonging to 116 species of ants, beetles, grasshoppers, and spiders from mountain ranges in central and northern Pakistan to the limits and breadths of their geographic and temperature range. Across all species and taxonomic groups, we found strong relationships between thermal traits and elevational distributions both in terms of geography and temperature. The relationships were robust when repeating the analyses for ants, grasshoppers, and spiders but not for beetles. These results indicate a strong role of physiology in determining elevational distributions of arthropods in Southern Asia. Overall, we found strong support for the climatic variability hypothesis and the climatic extreme hypothesis. A close association between species' distributional limits and their thermal tolerances suggest that in case of a failure to adapt or acclimate to novel climatic conditions, species may be under pressure to track their preferred climatic conditions, potentially facing serious consequences under current and future climate change.

Analysis of Tolfenamic Acid using a Simple, Rapid, and Stabilityindicating Validated HPLC Method.

BACKGROUND: Tolfenamic acid (TA) belongs to the fenamates class of non-steroidal anti-inflammatory drugs. Insufficient information is available regarding the availa-bility of a reliable and validated stability-indicating method for the assay of TA. OBJECTIVE: A relatively simple, rapid, accurate, precise, economical, robust, and stability-indicating RP-HPLC method has been developed to determine TA in pure and tablet dosage forms. METHODS: The method was validated according to the ICH guideline, and parameters like linearity, range, selectivity, accuracy, precision, robustness, specificity, and solution stability were determined. TLC and FTIR spectrometry were used to ascertain the purity of TA. The specificity was determined with known impurities and after performing forced degradation, while the robustness was established by Plackett-Burman's experimental design. The mobile phase used for the analysis was acetonitrile and water (90:10, v/v) at pH 2.5. The detection of the active drug was made at 280 nm using a C18 column (tR = 4.3 min.). The method's ap-plicability was also checked for the yellow polymorphic form of TA. RESULTS: The results indicated that the method is highly accurate (99.39-100.80%), precise (<1.5% RSD), robust (<2% RSD), and statistically comparable to the British Pharmacopoeia method with better sensitivity and specificity. CONCLUSION: It was observed that the stress degradation studies do not affect the method's accuracy and specificity. Hence the proposed method can be used to assay TA and its tablet dosage form.

Cliniciopathological Spectrum of Skin and Soft Tissue Swellings at a Tertiary Care Hospital of Lahore, Pakistan.

Background Skin and soft tissue swellings (SSTS) frequently present in dermatology, plastic surgery, and general surgery departments. While a general surgeon can take care of excisable lesions, people typically seek plastic surgery for cosmetic reasons. According to the signs and symptoms, soft tissue and skin lesions must be removed, and it is crucial to maintain cosmesis following their removal. Objective The aim of this article is to describe the clinical and histopathological types, sites, laterality, and postoperative complications of SSTS. Material and methods This retrospective study was conducted at the Department of Plastic and Reconstructive Surgery, Lahore General Hospital, Lahore, Pakistan in November 2022. We studied admitted patients from July 1, 2020 to June 30, 2022 for SSTS excision. Data on patients' demographics, associated features of SSTS, and their postoperative complications was gathered using Google Docs-generated proforma and sent to a statistician for the computation of results via a Microsoft Excel-generated spreadsheet. Results Out of the total 60 patients, 66.7% of the lesions were found in women. The mean age at presentation came out to be 34.16±17.42 years. Nevi with 16.7% were the most common SSTS in our study. The most common site of presentation of SSTS was the scalp and face in 63.3% of cases. Fever was the most frequently encountered post-excision complication in 40% of patients. Conclusion A comprehensive history, clinical examination, signs and symptoms, and the histology of the lesion, all play a crucial role in the management of such swellings. Surgery was the definitive treatment option for SSTS. There were very few major complications in a handful of patients.

Pharmaceutical based cosmetic serums.

The growth and demand for cosmeceuticals (cosmetic products that have medicinal or drug-like benefits) have been enhanced for the last few decades. Lately, the newly invented dosage form, i.e., the pharmaceutical-based cosmetic serum has been developed and widely employed in various non-invasive cosmetic procedures. Many pharmaceutical-based cosmetic serums contain natural active components that claim to have a medical or drug-like effect on the skin, hair, and nails, including anti-aging, anti-wrinkle, anti-acne, hydrating, moisturizing, repairing, brightening and lightening skin, anti-hair fall, anti-fungal, and nail growth effect, etc. In comparison with other pharmaceutical-related cosmetic products (creams, gels, foams, and lotions, etc.), pharmaceutical-based cosmetic serums produce more rapid and incredible effects on the skin. This chapter provides detailed knowledge about the different marketed pharmaceutical-based cosmetic serums and their several types such as facial serums, hair serums, nail serums, under the eye serum, lip serum, hand, and foot serum, respectively. Moreover, some valuable procedures have also been discussed which provide prolong effects with desired results in the minimum duration of time after the few sessions of the serum treatment.

Intervene to Improve: Awareness of Testicular Self-Examination and Testicular Cancer Among Male Patients at a Tertiary Care Hospital in Lahore, Pakistan.

Background and objective Testicular cancer is the commonest of all types of cancer males are affected with. Testicular cancer, when diagnosed early, has one of the best prognoses. However, in Pakistan, early detection is hindered by religious and sociocultural norms, lack of education, and awareness deficit. Testicular self-examination (TSE) can significantly facilitate early detection of the condition and decrease associated mortality rate. This study aimed to acquire the frame of mind regarding testicular cancer (TC) and testicular self-examination (TSE) among the male outdoor patients of Lahore General Hospital, Lahore. Materials and methods After ethical considerations, elaborated literature review and consequent pilot study were done to develop a bilingual questionnaire. Following patient consent, answers to a set of questions were noted down by the authors. A 90-second bilingual, motivational video was displayed and an educational pamphlet on the same topic was also handed over. Afterward, another survey was conducted to grasp the comprehension, satisfaction, and willingness to spread the message. Results About 92% of the subjects had not heard of or performed TSE and 58.3% mentioned lack of education as the reason for not knowing the method. Eighty-two percent patients had never heard of TC. Post-education, 100% patients claimed that their knowledge of the subject improved and 97% were ready to teach other male relatives. Conclusion The results indicate that the population's lack of awareness regarding testicular self-examination and testicular cancer is alarming. Most subjects did not know the age group, risk factors, presentation, and early prevention of testicular cancer.

Association of single nucleotide polymorphisms in heat stress protein 70 (HSP70) and 90 (HSP90) with the susceptibility of Pakistani sheep breeds to hemoparasitic infections.

The present study was designed to report the genotypic and allelic frequency of single nucleotide polymorphism (SNP) at 222 G > A in HSP70 and at ex6-7390T22G in the HSP90 gene of 204 sheep (Baluchi = 11, Kajli = 29, Latti = 06 and Mundri = 158) enrolled from District Rajanpur in Punjab and to report the susceptibility of these sheep to the blood-borne parasitic infection. The tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) approach revealed a significant variation (p < 0.001) in the genotype frequency of four enrolled sheep breeds at SNP 222 G > A in the HSP70 gene while the allelic frequency remained unaffected (p = 0.08). In all sheep breeds, GG (wild) genotype was most common. T-ARMS-PCR analysis revealed a similar trend for ex6-7390T22G in the HSP90 gene and it was observed that sheep had significantly higher wild-type (GG) (p < 0.05) at the studied SNPs. Studied epidemiological factors (sex and sampling sites) were not found associated with both SNPs. Chi-square test revealed that no specific genotype and allelic frequency at 222 G > A in HSP70 and at ex6-7390T22G in the HSP90 gene of the enrolled sheep breed was associated with the susceptibility to blood-borne parasitic infection (p > 0.05). In conclusion, we are reporting that Pakistan is blessed to have majority of sheep, from all breeds, having wild genotype at analyzed SNPs in heat stress genes. We highly recommend the genotypic screening of sheep before their selection as breeders to reduce the possibility of having sheep with polymorphic genotypes at 222 G > A in HSP70 and at 7390T22G in HSP90 genes that will improve the profitability and sustainability of animal production systems in Pakistan.

Nanosponges-based Drug Delivery System for the Cosmeceutical Applications of Stabilized Ascorbic Acid.

BACKGROUND: L-Ascorbic acid (AA) is a highly unstable compound, thus, limiting its use in pharmaceutical and cosmetic products, particularly at higher concentrations. OBJECTIVE: This study aimed to stabilize the highly sensitive molecule (AA) by encapsulating it in ß- cyclodextrin nanosponges (ß-CD NS) that can be used further in preparing cosmeceuticals products with higher AA concentrations and enhanced stability. METHODS: The NS has been synthesized by the melting method. The AA was encapsulated in ß-CD NS by the freeze-drying process. The prepared NS were characterized by FTIR spectrometry, SEM, Atomic Force Microscopy (AFM), zeta sizer, Differential Scanning Calorimetry (DSC), and the physical flow characteristics were also studied. The in vitro drug release was carried out on the Franz apparatus using a combination of two methods: sample & separate and dialysis membrane. The assay was performed using a validated spectrometric method. RESULTS: The entrapment efficiency of AA in ß-CD NS indicated a good loading capacity (83.57±6.35%). The FTIR, SEM, AFM, and DSC results confirmed the encapsulation of AA in ß-CD NS. The particle size, polydispersity index, and zeta potential results ascertained the formation of stabilized monodisperse nanoparticles. The physical flow characteristics showed good flow properties. Around 84% AA has been released from the NS in 4 h following the Korsmeyer-Peppas model. The AA-loaded NS remained stable for nine months when stored at 30±2°C/65±5% RH. CONCLUSION: It is concluded that the prepared NS can protect the highly sensitive AA from degradation and provide an extended-release of the vitamin. The prepared AA-loaded ß-CD NS can be used to formulate other cosmeceutical dosage forms with better stability and effect.

Practices of Informed Consent for Emergency Procedures at a Tertiary Care Hospital in Lahore, Pakistan.

Background The purpose of obtaining informed consent is to ensure that patients undergoing any medical or surgical intervention are neither deceived nor coerced. Accurately estimating surgical risks is critical for shared decision-making and informed consent. Probable complications and alternative procedures should be presented to the patient so that they can freely choose an operative option. However, this factor is difficult to carry on in emergencies where an urgent decision is required. Objective This study aimed to assess the ongoing clinical practices of informed consent in emergency surgeries at a tertiary care facility. Materials and methods A cross-sectional survey was carried out from March 2022 to June 2022 at the Department of General Surgery, Lahore General Hospital, Lahore, Pakistan, with patients who had undergone surgical procedures under local, spinal, or general anesthesia within 24 hours of presentation. A Google Form (Google Inc., Mountainview, CA) was designed, containing a predefined set of 32 standard questions, and patients were interviewed in their native language to assess their satisfaction regarding the pattern and components of emergency informed consent. Categorical data were assessed using measures of central tendency, frequencies, and percentages. Results A total of 169 patients were selected for the study. Only 1.6% of them signed the consent form themselves, while 93.5% of the forms were signed by their first-degree relatives. Verbal consent was taken in 4.8% of cases. In 88% of cases, informed consent was obtained by the house surgeons. The majority of patients, i.e., 78.2%, were not able to read the written consent form; however, 83.1% understood the verbal information. About 66.3% of patients agreed that they were informed about the nature of their disease, while 67.5%, 14.8%, and 13.7% affirmed that they were explained the nature of surgical intervention, associated risks, and type of anesthesia, respectively. Overall, 59.5% of patients felt satisfied with the process of informed consent. About 91.1% of the patients believed that their decisions were unaffected by the procurement of informed consent. Conclusion The existing practices of informed consent and comprehension by the population were found to be substandard. Physicians seem to ignore bioethics, and patients appear to be unaware of their basic rights. Although practiced at our center, not all components of informed consent were communicated to the patients. The risks of the procedures and the mode of anesthesia used were not well addressed by doctors. There is a grave need to educate the medical community about the legal and ethical aspects of informed consent, as well as the public masses regarding their rights.

Significance of Histopathology of Appendectomy Specimens: Analysis From a Teaching Hospital of Pakistan.

Background Histopathology of a tissue specimen plays a crucial role in formulating the final diagnosis of any disease. It confirms whether the histopathological findings are in correspondence with the clinical diagnosis and thus suggests an optimal management plan. Standard surgical practices guide that every human tissue specimen must undergo postoperative tissue analysis unless indicated otherwise. Objective To determine the significance of histopathology in determining the final diagnosis of appendectomy specimens. Materials and methods This retrospective clinical study conducted in May 2022 included 100 patients operated for appendectomy from January 1, 2021, to December 31, 2021, in the emergency room of the Department of General Surgery, Unit-III, Lahore General Hospital, Lahore. Data were retrieved from patients' records and the picture archiving and communication system (PACS). A Google Forms-based pro forma (Google, Mountain View, CA) was generated to include the demographic details, clinical manifestations, and histopathology reports of the patients. Descriptive analysis was completed using a Microsoft Excel spreadsheet (Microsoft Corporation, Redmond, WA). Results Fifty-two patients were females out of the total 100. The mean age at presentation was 23.02 ± 12.02 years. Of the samples, 54% were not sent for histopathology. Among the remaining ones, 27% of cases were proven to be acute appendicitis. Alvarado score was 7-10 in 50% of patients. Other lesions proven by histopathology were appendiceal phlegmon (4%), perforated appendix (4%), mucocele (1%), carcinoid tumor (1%), tuberculosis (1%), and adenocarcinoma (1%). Conclusions Histopathological analysis is the gold standard for the tissue diagnosis of a disease. The high percentage of the samples not sent for histopathology is alarming since the appendix is not only a site for inflammatory pathologies but for neoplastic lesions as well. This practice depicts that the incidence of non-inflammatory pathologies is being ignored by healthcare professionals and there is a dire need to emphasize the significance of acquiring histopathology reports for the specimens of appendectomy in all circumstances.

Tsallis Entropy for Loss Models and Survival Models Involving Truncated and Censored Random Variables.

The aim of this paper consists in developing an entropy-based approach to risk assessment for actuarial models involving truncated and censored random variables by using the Tsallis entropy measure. The effect of some partial insurance models, such as inflation, truncation and censoring from above and truncation and censoring from below upon the entropy of losses is investigated in this framework. Analytic expressions for the per-payment and per-loss entropies are obtained, and the relationship between these entropies are studied. The Tsallis entropy of losses of the right-truncated loss random variable corresponding to the per-loss risk model with a deductible d and a policy limit u is computed for the exponential, Weibull, χ2 or Gamma distribution. In this context, the properties of the resulting entropies, such as the residual loss entropy and the past loss entropy, are studied as a result of using a deductible and a policy limit, respectively. Relationships between these entropy measures are derived, and the combined effect of a deductible and a policy limit is also analyzed. By investigating residual and past entropies for survival models, the entropies of losses corresponding to the proportional hazard and proportional reversed hazard models are derived. The Tsallis entropy approach for actuarial models involving truncated and censored random variables is new and more realistic, since it allows a greater degree of flexibility and improves the modeling accuracy.

Predicting Compressive and Splitting Tensile Strengths of Silica Fume Concrete Using M5P Model Tree Algorithm.

Compressive strength (CS) and splitting tensile strength (STS) are paramount parameters in the design of reinforced concrete structures and are required by pertinent standard provisions. Robust prediction models for these properties can save time and cost by reducing the number of laboratory trial batches and experiments needed to generate suitable design data. Silica fume (SF) is often used in concrete owing to its substantial enhancements of the engineering properties of concrete and its environmental benefits. In the present study, the M5P model tree algorithm was used to develop models for the prediction of the CS and STS of concrete incorporating SF. Accordingly, large databases comprising 796 data points for CS and 156 data records for STS were compiled from peer-reviewed published literature. The predictions of the M5P models were compared with linear regression analysis and gene expression programming. Different statistical metrics, including the coefficient of determination, correlation coefficient, root mean squared error, mean absolute error, relative squared error, and discrepancy ratio, were deployed to appraise the performance of the developed models. Moreover, parametric analysis was carried out to investigate the influence of different input parameters, such as the SF content, water-to-binder ratio, and age of the specimen, on the CS and STS. The trained models offer a rapid and accurate tool that can assist the designer in the effective proportioning of silica fume concrete.

Acute and subacute toxicity studies of a poly herbal formulation used for diabetes.

Objectives: PHF-dia (Poly Herbal Formulation Diabetes) is a polyhedral formulation possessing antihyperglycemic and antihyperlipdimic effects. This study aims to assess acute and sub-acute toxicity of PHF-dia in rats. Methods: This is an experimental study conducted in two different phases. Acute toxicity was conducted for 14 days and sub-acute toxicity was conducted for 28 days. Both studies were conducted in animal house of Jinnah University for Women, Karachi, Pakistan. Acute toxicity was evaluated in vivo with single time oral administration of 400 mg/kg and 2000 mg/kg doses for two weeks. Sub-acute toxicity was investigated with the application of repeated doses of 150 mg/kg/day, 250 mg/kg/day and 500 mg/kg/day for 28 days. Results: Acute toxicity study results showed no toxic symptoms, behavioral changes or death in rats up to 2000 mg/kg. Therefore, LD50 of oral toxic dose must be more than 2000 mg/ml. Similarly, sub-acute toxicity studies confirmed the safety of PHF-dia and showed no clinical symptoms nor biochemical or histological variation in rats treated with 150 mg/kg, 250 mg/kg and 500 mg/kg compared to the control group (p <0.05). Conclusion: This indicates safe nature of PHF-dia for the further clinical trials. However, mechanism of action of PHF-dia is not fully understood.

Quantifying the effect of waste on soil health in European Union: what are the roles of technology, natural capital, and institutional quality?

With a surge in both hazardous and non-hazardous waste in recent decades, European Union countries are losing their soil quality which in turn affects the agricultural production of their economies. Taking this into account, this study presents the effect of hazardous and non-hazardous waste, plastic waste, and electronic waste on soil health for 24 European Union (EU) countries during 2004-2018 period. The impacts of several other variables such as technological innovation, ICT, natural capital, fossil fuel energy consumption, and institutional quality on soil health are also examined. To achieve the above objectives, we employ Driscoll-Kraay technique as the main methodology as well as panel spatial correlation consistent (PSCC) standard errors and quantile estimation at median. The results demonstrate that electronic waste has a negative effect on soil health while the effect of total hazardous and non-hazardous waste and plastic waste on soil health remains insignificant. Technological innovation, ICT, and institutional quality, as well as fossil fuel energy consumption, have positive impacts on soil health. Furthermore, natural capital moderates the effect of plastic and electronic waste on soil health. The study finally provides precise policy recommendations for the EU countries such as proper handling of wastes, promoting strong institutional quality as well as use of technology to enrich the soil nutrient balance.

Volatility Dynamics of Non-Linear Volatile Time Series and Analysis of Information Flow: Evidence from Cryptocurrency Data.

This paper aims to empirically examine long memory and bi-directional information flow between estimated volatilities of highly volatile time series datasets of five cryptocurrencies. We propose the employment of Garman and Klass (GK), Parkinson's, Rogers and Satchell (RS), and Garman and Klass-Yang and Zhang (GK-YZ), and Open-High-Low-Close (OHLC) volatility estimators to estimate cryptocurrencies' volatilities. The study applies methods such as mutual information, transfer entropy (TE), effective transfer entropy (ETE), and Rényi transfer entropy (RTE) to quantify the information flow between estimated volatilities. Additionally, Hurst exponent computations examine the existence of long memory in log returns and OHLC volatilities based on simple R/S, corrected R/S, empirical, corrected empirical, and theoretical methods. Our results confirm the long-run dependence and non-linear behavior of all cryptocurrency's log returns and volatilities. In our analysis, TE and ETE estimates are statistically significant for all OHLC estimates. We report the highest information flow from BTC to LTC volatility (RS). Similarly, BNB and XRP share the most prominent information flow between volatilities estimated by GK, Parkinson's, and GK-YZ. The study presents the practicable addition of OHLC volatility estimators for quantifying the information flow and provides an additional choice to compare with other volatility estimators, such as stochastic volatility models.

Exploring the dynamic relationship between financial development, renewable energy, and carbon emissions: A new evidence from belt and road countries.

This empirical study examines the endogenous relationship between carbon emissions (CO2), financial development, renewable energy, globalization, and institutional quality in 64 belt and road initiative countries (BRI) using a two-step system generalized method of moments (GMM) approach with panel data over the period 2003 to 2018. Furthermore, this study used (Dumitrescu & Hurlin, 2012) causality test to estimate the variables' causal relationship. The results indicate that financial development significantly increases CO2 emissions and causes environmental degradation in BRI countries. However, renewable energy and globalization mitigate CO2 emissions and improve the quality of the environment. Institutional quality was positive in correlation with CO2 emission and indicates bad governance, corruption, weak bureaucracy, and improper implementation of environmental laws cause environmental degradation. Further, the study also reports a bidirectional relationship of financial development, renewable energy, and institutional quality with CO2 emissions and a unidirectional causality running from globalization to CO2 emissions in BRI countries. This study offers policymakers insight into restructuring the financial system, energy consumption pattern, and global integration and improving institutions' quality for a sustainable environment and the economy at the national and regional levels.

A mini-review on the impact of COVID 19 on vital organs.

COVID-19 (Corona Virus Disease-2019) is an infectious disease caused by a novel coronavirus, known as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This is a highly contagious disease that has already affected more than 220 countries globally, infecting more than 212 million people and resulting in the death of over 4.4 million people. This review aims to highlight the pertinent documentary evidence upon the adverse effects of the SARS-CoV-2 infection on several vital human organs. SARS-CoV-2 primarily targets the lung tissue by causing diffuse alveolar damage and may result in Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 infects the cell via cell surface receptor, angiotensin-converting enzyme 2 (ACE2). Besides lungs, SARS-CoV-2 critically damage tissues in other vital human organs such as the heart, kidney, liver, brain, and gastrointestinal tract. The effect on the heart includes muscle dysfunction (acute or protracted heart failure), myocarditis, and cell necrosis. Within hepatic tissue, it alters serum aminotransferase, total bilirubin, and gamma-glutamyl transferase levels. It contributes to acute kidney injury (AKI). Localized infection of the brain can lead to loss or attenuation of olfaction, muscular pain, headaches, encephalopathy, dizziness, dysgeusia, psychomotor disorders, and stroke; while the gastrointestinal symptoms include the disruption of the normal intestinal mucosa, leading to diarrhea and abdominal pain. This review encompassed a topical streak of systemic malfunctions caused by the SARS-CoV-2 infection. As the pandemic is still in progress, more studies will enrich our understanding and analysis of this disease.

Moderating the effect of globalization on financial development, energy consumption, human capital, and carbon emissions: evidence from G20 countries.

The policy debate on the financial development and dynamic of carbon dioxide (CO2) emission is topical. Globalization can affect this relationship by making financial investments in green energy and environment-friendly technology, as environmental sustainability is the primary concern for modern society. This study proposes a newly formulated conceptual framework to explore globalization's moderating role on exoplanetary variables (financial development, energy consumption, human capital, and gross domestic product) and CO2 emission. We employed Fixed Effect Ordinary Least Squares (FE-OLS), Driscoll-Kraay standard error approach (D-K), and Dumitrescu and Hurlin's (2012) panel causality test. Our sample of the study comprised full and subsamples of G20 countries (excluding the European Union) from 1986 to 2018. The results indicated that financial development and human capital decreased carbon emissions, while GDP and energy consumption substantially increased carbon emissions during the study time. Further, globalization moderated the positive impact of financial development and human development on carbon emissions. A sustainable environmental agenda is achieved by a stronger financial system, encouraging green finance, and including technical education that improves production efficiency. However, globalization moderated the negative impact of energy consumption and GDP on carbon emission. Besides, we also reported the bidirectional causal relationship of GDP to energy consumption. Our empirical research provides new insights for policymakers and governments to formulate country-based policies to protect environmental quality while achieving sustainable economic goals.